Abstract The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Abstract Aims Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Methods and results In 18 924 patients with recent acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score–matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median of 8.3 months from randomization, after a median of 6.0 months with LDL-C <0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than those of the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C vs. 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047). Conclusion A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with a lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years. Trial registration ClinicalTrials.gov NCT01663402

Introduction: The commonest mitral regurgitation etiologies are degenerative (60%), rheumatic post-inflammatory, 12%) and functional (25%). Due to the large number of patients with acute MI, the incidence of ischaemic MR is also high. Ischaemic mitral regurgitation is a complex multifactorial disease that involves left ventricular geometry, the mitral annulus, and the valvular/subvalvular apparatus. Ischaemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Research Objectives: The objective of this study is to determine the role of echocardiography in detecting and assessment of mitral regurgitation mechanism, severity, impact on treatment strategy and long term outcome in patients with myocardial infarction during the follow up period of 5 years. Also one of objectives to determine if the absence or presence of ischaemic MR is associated with increased morbidity and mortality in patients with myocardial infarction. Patients and methods: The study covered 138 adult patients. All patients were subjected to echocardiography evaluation after acute myocardial infarction during the period of follow up for 5 years. The patients were examined on an ultrasound machine Philips iE 33 xMatrix, Philips HD 11 XE, and GE Vivid 7 equipped with all cardiologic probes for adults and multi-plan TEE probes. We evaluated mechanisms and severity of mitral regurgitation which includes the regurgitant volume (RV), effective regurgitant orifice area (EROA), the regurgitant fraction (RF), Jet/LA area, also we measured the of vena contracta width (VC width cm) for assessment of IMR severity, papillary muscles anatomy and displacement, LV systolic function ± dilation, LV regional wall motion abnormality WMA, LV WMI, Left ventricle LV remodeling, impact on treatment strategy and long term mortality. Results: We analyzed and follow up 138 patients with previous (>16 days) Q-wave myocardial infarction by ECG who underwent TTE and TEE echocardiography for detection and assessment of ischaemic mitral regurgitation (IMR) with baseline age (62 ± 9), ejection fraction (EF 41±12%), the regurgitant volume (RV) were 42±21 mL/beat, and effective regurgitant orifice area (EROA) 20±16 mm2, the regurgitant fraction (RF) were 48±10%, Jet/LA area 47±12%. Also we measured the of vena contracta width (VC width cm) 0,4±0,6 for assessment of IMR severity. During 5 years follow up, total mortality for patients with moderate/severe IMR–grade II-IV (54.2±1.8%) were higher than for those with mild IMR–grade I (30.4±2.9%) (P<0.05), the total mortality for patients with EROA ≥20 mm2(54±1.9%) were higher than for those with EROA <20 mm2(27.2±2.7%) (P<0.05), and the total mortality for patients with RVol ≥30 mL (56.8±1.7%) were higher than for those with RVol<30ml (29.4±2.9%) (P<0.05). After assessment of IMR and during follow up period 64 patients (46%) underwent CABG alone or combined CABG with mitral valve repair or replacement. In this study, the procedure of concomitant down-sized ring annuloplasty at the time if CABG surgery has a failure rate around 24% in terms of high late recurrence rate of IMR during the follow period especially after 18–42 months. Conclusion: The presence of ischaemic MR is associated with increased morbidity and mortality. Chronic IMR, an independent predictor of mortality with a reported survival of 40–60% at 5 years. Ischaemic mitral regurgitation has important prognosis implications in patients with coronary heart disease. Recognizing the mechanism of valve incompetence is an essential point for the surgical planning and for a good result of the mitral repair. It is important that echocardiographers understand the complex nature of the condition. Despite remarkable progress in reparative surgery, further investigation is still necessary to find the best approach to treat ischaemic mitral regurgitation.

Reperfusion therapy remains the most effective treatment for patients suffering from acute coronary syndrome. The start time of reperfusion therapy is an important factor, and has a positive influence in reducing the number of days of hospitalisation, occurrences of readmi ssion, risk of reinfarction, and both short and long-term mortality. Several models of reperfusion therapy are available: thrombolytic treatment (pre-hospital or in-hospital), primary percutaneous coronary intervention (primary PCI [pPCI]), or a combination of both. PPCI is the preferred treatment (and should be administered as early as possible) in centres with experienced teams, especially for patients in cardiogenic shock, or those with contraindicated fibrinolytic (TL) therapies. Many randomised clinical trials have shown that pPCI is superior to TL in reducing mortality, reinfarction, and stroke. Our aim is to describe the easiest and quickest way of establishing the primary PCI network in Bosnia and Herzegovina. It is possible, by combining the efforts of both entities of Bosnia and Herzegovina, to establish a functional and effective PCI network, particularly since Bosnia and Herzegovina has become a participant in the Stent for Life initiative.

[Eur Heart J 2014;35:1957-1970, doi:10.1093/eurheartj/eht529] Figure 1 of this article contained …

AIMS Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. METHODS AND RESULTS A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. CONCLUSION Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encouraged.

The aim of this paper is to present the preliminary results of the monitoring study of the frequency of congenital heart disease in newborns in Tuzla Canton (Bosnia and Herzegovina), and their distribution by sex of the newborn and maternal age. The study used the data from the book of protocols and case records of the Clinic for Gynecology and Obstetrics, the University Clinical Center in Tuzla. The analysis of 8,521 newborns between 1 January 2007 and 31 December 2008 has resulted in the frequency of 1.76%, i.e. 1.31% for the mature newborns and 0.45% for the premature newborns respectively. Of the total number of registered anomalies, 10% was associated with congenital anomalies of other systems. No statistically significant differences were found in the subsamples of both mature and premature newborns when it comes to the distribution of congenital heart disease by sex of newborns and maternal age. The frequency registered in the analyzed period suggests the necessity of screening and monitoring congenital heart disease in the observed population.

Molecular-genetic methods allow direct assessment of genetic diversity at the level of diversity of DNA structures between individuals of the same type. Factors that may influence the association of alleles with disease, such as ethnic or gender effect, can’t be determined without allelic frequencies in populations. The aim of our study was to determine the frequency of gene alleles for the hemochromatosis and the gene for angiotensin converting enzyme in the Bosnian-Herzegovinian population. The goal of study of gene copy number of DAZ was to determine the frequency of partial DAZ gene deletions and to analyse the existence of duplications in the general Bosnian population. Akademija nauka i umjetnosti Bosne i Hercegovine Aкадемија наука и умјетности босне и Xерцеговине Academy of Sciences and Arts of Bosnia and Herzegovina Međunarodni naučni skup „Struktura i dinamika ekoSiStema dinarida – Stanje, mogućnoSti i perSpektive“ International Conference „StruCture and dYnamiCS oF eCoSYStemS dinarideS – StatuS, poSSiBiLitieS and proSpeCtS“ 15-16. juni/June 2011, Sarajevo, Bosnia and Herzegovina Posebna izdanja/Special Editions CXLIX Odjeljenje prirodnih i matematičkih nauka Department of Natural Sciences and Mathematics Zbornik radova/Proceedings 23, 89-97. DOI: 10.5644/proc.eco-03.05 2012 ISBN: 978-9958-501-81-4

BACKGROUND The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy was first described in Japan approximately 20 years ago (Satoh and coworkers, 1991). It was later described elsewhere as well and is being increasingly recognized. Takotsubo Cardiomyopathy characterized by transient apical and midventricular LV dysfunction in the absence of significant coronary artery disease that is triggered by emotional or physical stress. Its name refers to a contraption used for catching octopuses and suggests the aspect assumed by the ventricle during the systole due to the typical regional wall motion abnormalities that occur after onset. Takotsubo cardiomiopathy occurring mainly in post-menopausal women, echocardiography in the Takotsubo cardiomyopathy reveals during its acute phase a ballooning resembling the octopus trap configuration--the apex and lateral ventricular segments are hypokinetic while the base is hyperkinetic--along with reduced ejection fraction. Ventricular function will usually recover within a few days/weeks. OBJECTIVE AND PURPOSE The objective of this study is to determine the role of echocardiography in detecting and establishing the diagnosis of Takotsubo cardiomiopathy in patients with suspect acute coronary syndrome and during the follow up period. PATIENTS AND METHODS The study covered 12 adult patients the majority are women (92%) who were subjected to echocardiography evaluation as part of the clinical cardiological examination due to suspect acute coronary syndrome or Takotsubo Stress Cardiomyopathy. The patients were examined on an ultrasound machine Philips iE 33 x Matrix, ATL HDI and GE Vived 7 equipped with all cardiologic probes for adults and multi-plan TEE probes. We evaluated clinical characteristics, LV systolic function, biomarkers, and prognosis in all patients. RESULTS Among all the patients referred for Echocardiographic evaluation for left ventricle motion abnormalities with suspect acute coronary syndrome, the echo exam revealed 12 patients with acute apical ballooning which involving the left ventricular apex and med-ventricle. The triggering factors were physical stress in 4 patients (33%) and emotional stress in 8 patients (67%). The initial symptom was chest pain (n = 8, 67%) rather than dyspnea (n = 4, 33%). An initial electrocardiogram (EKG) presented ST-elevation (n = 10, 83%) and T-wave inversion (n = 2, 17%), other data are shown on Table 2. Among the all patients 8 of them (66%) had normal EF by the 1st follow up (47 +/- 51 days), and the rest 4 patients (34%) had normal EF by 68 +/- 96 days. CONCLUSION Widespread uses of echocardiography has contributed to more frequent recognition of Takotsubo stress cardiomyopathy and highlight the central role of this noninvasive method from an echocardiographers' perspective.

Direct coronary stenting in reducing radiation and radiocontrast consumption Introduction. Coronary stenting is the primary means of coronary revascularization. There are two basic techniques of stent implantation: stenting with balloon predilatation of stenosis and stenting without predilatation (direct stenting). Limiting the time that a fluoroscope is activated and by appropriately managing the intensity of the applied radiation, the operator limits radiation in the environment, and this saves the exposure to the patient and all personnel in the room. Nephrotoxicity is one of the most important properties of radiocontrast. The smaller amount of radiocontrast used also provides multiple positive effects, primarily regarding the periprocedural risk for the patients with the reduced renal function. The goal of the study was to compare fluoroscopy time, the amount of radiocontrast, and expenses of material used in direct stenting and in stenting with predilatation. Patients and methods. In a prospective study, 70 patients with coronary disease were randomized to direct stenting, or stenting with predilatation. Results. Fluoroscopy time and radiocontrast use were significantly reduced in the directly stented patients in comparison to the patients stented with balloon-predilatation. The study showed a significant reduction of expenses when using a direct stenting method in comparison to stenting with predilatation. Conslusions. If the operator predicts that the procedure can be performed using direct stenting, he is encouraged to do so. Direct stenting is recommended for all percutaneous coronary interventions when appropriate conditions have been met. If direct stenting has been unsuccessful, the procedure can be converted to predilatation.

Despite aggressive antiplatelet therapy in the setting of percutaneous coronary intervention, the incidence of stent thrombosis remains approximately 0.5% to 0.8%. We report on a 53-year-old male patient with recurrent coronary stent thrombosis treated by coronary re-interventions and anticoagulation. Initial diagnostic selective coronary angiography revealed 90% proximal circumflex coronary artery stenosis in a patient with 3rd degree of stabile angina by Canadian Cardiology Society classification. After premedication with a loading dose of 600 mg clopidogrel, 300 mg aspirin and intravenous enoxaparine 1 mg/kg, a bare-metal stent was implanted. The initial postprocedural course was normal. On the third day after the intervention, the patient was subjected to reintervention because of the stent thrombosis, and on the fifth day after reintervention – to the third percutaneous coronary angioplasty, also because of the stent thrombosis. Clopidogrel resistence was suspected and treatment with warfarin was initiated, after which there were no new cardiac events. Three months later, anticoagulation was discontinued, and as an antiplatelet agent aspirin 100 mg daily remained in therapy. Up to now (one-year), follow-up of the patient has been uneventful. In the case of suspected clopidogrel resistance, alternative therapeutic options have to be considered, like introducing per os anticoagulation (e.g. warfarin), introducing ticlopidin instead of clopidogrel, or, in the near future, possibly introducing prasugrel, a similar agent currently in transition from investigation into clinical use.

Objective The purpose of this randomized study was to evaluate the effect on graft patency by adding clopidogrel to aspirin in off-pump coronary artery bypass (OPCAB) grafting and the possible side effects of such therapy. Methods Twenty patients who underwent standard OPCAB through median sternotomy were randomized immediately after surgery in two groups. Patients in group A (n = 10) received 100 mg of aspirin starting preoperatively, continuing indefinitely. Patients in group B received 100 mg of aspirin and, in addition, 75 mg of clopidogrel starting immediately after the operation and for 3 months. Postoperative bleeding and other perioperative parameters were compared. Angiography was repeated 3 months after surgery to determine the patency and quality of grafts. Results Preoperative risk factors were similar in the two groups. There was no significant difference in average number of distal anastomosis (P = 0.572), operation time (P = 0.686), postoperative bleeding (P = 0.256), ventilation time (P = 0.635), and intensive care unit stay (P = 0.065). Length of stay was shorter in group B (P = 0.024). There was no postoperative complication in either groups. Eight of 27 grafts in group A and 2 of 29 grafts in group B (P = 0.037) were occluded at the time of control angiography. Conclusions Early administration of a combined regimen of clopidogrel and aspirin after OPCAB grafting is not associated with increased postoperative bleeding or other major complications. Despite the small number of patients in this study and small number of examined grafts, the results suggest that the addition of clopidogrel may increase graft patency after OPCAB grafting.